We propose to attempt to extend our basic understanding of the way histones are organized on the DNA molecule. We plan to probe the conformation of the histone molecules with respect to the two strands of DNA, to analyze if the entire length or only a part of the DNA molecule interacts with histone. Further we will study the orientation of histone molecules with respect to immediately adjacent histones, asking for instance whether they are found back to back in the major groove, or on the other hand, they may be arranged primarily end to end with a variable degree of overlap. The organization of histones on DNA will be studied by DNA-ase treatment with an analysis of the single stranded material which appears to be the primary product. In addition covalent fixation of histones to DNA by formaldehyde and of histones to adjacent histones by glutaraldehyde may provide additional clues as to the nature of the various interactions. Finally, density gradient separation of fixed nucleoprotein will be exploited in an attempt to isolate fractions of chromosomal material either enriched or depleted in histone relative to the mean histone complement.